Intranasal Administration of the SUR1 inhibitor Glibenclamide for the Treatment of Traumatic Brain Injury

• Published in: Proceedings for Annual Meeting of The Japanese Pharmacological Society Vol. WCP2018; p. PO2-1-18
• Main Authors: Song, Mingke, Wang, Ju, Chen, Jin, Xu, Xin-Lu, Yu, Qi
• Format: Journal Article
• Language: English
• Published: Japanese Pharmacological Society 2018
• Subjects: Glibenclamide; Intranasal delivery; Traumatic Brain Injury
• ISSN: 2435-4953; 2435-4953
• DOI: 10.1254/jpssuppl.WCP2018.0_PO2-1-18

Traumatic Brain Injury (TBI) is a leading cause of human death and disability worldwide. Animal studies show that TBI induces upregulation of the sulfonylurea receptor isoform 1 (SUR1)-regulated NCCa-ATP (SUR1-TRPM4) channels in neurons, astrocytes and capillary endothelial cells. Some preclinical data show that subcutaneous administration of the SUR1 inhibitor glibenclamide can reduce the secondary brain damage after TBI. In many TBI cases, however, the intravenous delivery is infeasible because peripheral blood circulation is disrupted by shock. In contrast, nasal delivery provides a noninvasive method to bypass the blood brain barrier (BBB) and directly transport drugs to the cortex through the nasal cavity and the olfactory bulb of the brain. In this study, we constructed a mouse TBI mode by using a controlled cortical impact injury (CCI) device and conducted intranasal delivery of glibenclamide to mice at 15, 60,120 and 360 min after the onset of TBI. The ensuing administration of glibenclamide was performed twice daily for 7 days. At 24 hours after CCI injury, glibenclamide significantly reduced brain edema assessed by the percentage change in water content of brain tissues. The contusion volume at 24 hours also significantly decreased in glibenclamide-treated mice. Therefore, intranasal administration of the SUR1 inhibitor glibenclamide can prevented brain damage in our experimental setting. Currently, we are using more animals to examine whether glibenclamide could improve recovery of the sensorimotor function. (This work was supported by the National Natural Science Foundation of China No. 81671375 and Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine).